title: Cyclic hydroxamic acid inhibitors of prostate cancer cell growth: selectivity and structure activity relationships.
abstract: BACKGROUND
  Clinical symptoms of prostatitis, prostatodynia, and benign prostatic hyperplasia are relieved by the pollen extract cernilton, and the water-soluble fraction of this extract selectively inhibits growth of some prostate cancer cells. A cyclic hydroxamic acid, DIBOA, has been isolated from this extract and mimics its cell growth-inhibitory properties, but the specificity of DIBOA for inhibition of prostate cell growth has not been reported.
  
  
  METHODS
  The in vitro growth inhibitory effects of DIBOA and nine structurally related compounds on DU-145 prostate cancer cells, MCF-7 breast cancer cells, and COS-7 monkey kidney cells were determined by treatment of the cells with various concentrations of the compounds for 2-6 days.
  
  
  RESULTS
  The compounds exhibited a wide range of potencies, but none of them exhibited selective inhibition of DU-145 cell growth. MCF-7 cells were more sensitive to DIBOA than either DU-145 cells or COS-7 cells. 3,4-dihydroquinoline-2(1H)-one, compound (4), and 1-hydroxy-6-chloro-3,4-dihydroquinolin-2(1H)-one, compound (7), selectively inhibited MCF-7 cell growth at a concentration of 10 micrograms/ml. 1-hydroxy-3,4-dihydroquinolin-2(1H)-one, compound (3), and compound 7 were the most potent inhibitors of DU-145 cell growth. Treatment of DU-145 cells with 3 (100 micrograms/ml) substantially decreased the number of viable cells within 2 days, and no viable cells remained in the culture by day 4.
  
  
  CONCLUSIONS
  It is unlikely that DIBOA, compound (1), is responsible for the selective growth inhibition of prostate cancer cells by the water-soluble fraction of the pollen extract cernilton. Cell morphology results indicate that the growth-inhibitory effects of DIBOA and structurally related agents on DU-145 cells are due to their ability to cause cell death.
authors.affiliation: Department of Urologic Surgery, University of Minnesota, Minneapolis, USA.
authors.forename: K P
authors.initials: KP
authors.lastname: Roberts
authors.forename: R A
authors.initials: RA
authors.lastname: Iyer
authors.forename: G
authors.initials: G
authors.lastname: Prasad
authors.forename: L T
authors.initials: LT
authors.lastname: Liu
authors.forename: R E
authors.initials: RE
authors.lastname: Lind
authors.forename: P E
authors.initials: PE
authors.lastname: Hanna
mesh_terms: D048588:Benzoxazines; D001943:Breast Neoplasms / Q000473:pathology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007668:Kidney / Q000166:cytology; D008297:Male; D010078:Oxazines / Q000737:chemistry / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000473:pathology*; D013329:Structure-Activity Relationship; D013997:Time Factors; D014407:Tumor Cells, Cultured
chemical_list: D048588:Benzoxazines; D010078:Oxazines; C104846:2,4-dihydroxy-1,4-benzoxazin-3-one